Human atrial natriuretic peptide (ANP) is a 28-amino acid polypeptide (human ANP 99-126), which was discovered at the end of 1983 [1] and the beginning of 1984 [2]. ANP is a polypeptide hormone released from the cardiac atria in response to artial stretch and plays an important role in the regulation of body fluid homeostasis [3]. ANP's receptor, natriuretic peptide receptor-A (NPR-A) is expressed on cells in many different tissues of various organ systems and signals through guanylyl cyclase. Both ANP and NPR-A are expressed by lung cancer cells, and oversecretion of ANP has been linked with hyponatremia (14-16). Recently, the inventors' laboratory determined that the expression and signaling of NPR-A is important for tumor growth and could be a new target for cancer therapy [4]. Blocking NPR-A signaling through treatment with nanoparticles conjugated with siNPRA or pNP73-102 attenuated tumorigenesis in lung and ovarian cancers and melanomas by several mechanisms, including decreasing local inflammation, inducing the expression of tumor suppressive gene Rb, and blocking vascular endothelial growth factor (VEGF) expression. NPR-A appears to be expressed largely in restricted cell populations containing high levels of ANP. Other studies implicated that the NPR-A receptor is related mainly to the autoregulation of ANP neurons and central control of cardic ANP release [5]. It was also reported that ANP-activated cGMP synthesis provided a good index of NPR-A protein expression, which ranges from maximal in adrenal gland, lung, kidney, and testis to minimal in heart and colon [6]. The disruption of ANP-NPR-A signaling inhibits tumor burden and metastasis.
Molecularly imprinted polymers (MIPs) are synthetic materials produced through cross-linking the functional monomers in the presence of the template molecules. Following removal of the template, the cavities possessing size, shape, and functional group orientation which are complementary to the target molecules are generated [7,8]. The major templates for MIPs have characterized low molecular weight in organic solvents, whereas the aqueous molecular imprinting biomolecules such as peptide and proteins still remains elusive. The main difficulties to imprint the large and flexible proteins include the large molecular dimensions, the flexibility of the chain and low mass-transfer kinetics which limit the polymer molecular recognition capacity and selectivity. A number of different strategies for creating MIP nanoparticles targeting proteins and peptides have been developed. Utilizing functional groups to form strong template interactions such as electrostatic and metal-chelating have been used [9, 10]. For example, MIP nanoparticles synthesis with a functional monomer optimization strategy using hydrophobic and electrostatic function could possess the binding affinity and selectivity for the biological target comparable to those of natural antibodies [11]. The epitope approach using a small sequence of amino acids from the large protein target has been used to create the imprint. The resulting MIP by the epitope approach can successfully bind oxytocin by imprinting Tyr-Pro-Leu-Gly (SEQ ID NO:1) amino acid sequence [12, 13]. Such particles have recently been studied as functional materials for antibodies for capturing and neutralizing toxin peptide [11, 14, 15], protein selective separation and discrimination [16].